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Equine veterinary journal2009; 41(7); 693-699; doi: 10.2746/042516409x436286

In vivo effects of meloxicam on inflammatory mediators, MMP activity and cartilage biomarkers in equine joints with acute synovitis.

Abstract: Meloxicam is a commonly used nonsteroidal anti-inflammatory drug in equine practice, but little is known about its in vivo effects on joint inflammation and cartilage turnover. Objective: To study the effects of meloxicam on biomarkers of inflammation, matrix metalloproteinase (MMP) activity, and cartilage biomarkers in joints with experimental synovitis. Methods: In a 2-period cross-over study, synovitis was induced at T = 0 h in the L or R intercarpal joint of 6 horses by intraarticular injection of 0.5 ng lipopolysaccharide (LPS). Horses received once daily meloxicam (0.6 mg/kg bwt per os) or placebo starting at post injection hour (PIH) 2, and clinical evaluations as well as blood and synovial fluid (SF) sampling were performed at PIH 0, 8, 24 and 168. Synovial fluid was analysed for prostaglandin E2, bradykinin, substance P, general MMP activity, glycosaminoglycans (GAG), CS846 epitope, type II collagen cleavage fragments (C2C) and type II collagen carboxypropeptide (CPII). Concentrations in meloxicam- vs. placebo-treated joints over time were compared using a linear mixed model. Results: Lipopolysaccharide injection caused marked transient synovitis without systemic effects. Meloxicam caused a significant reduction in lameness at PIH 8 and 24 and tended to reduce effusion. In addition, meloxicam significantly suppressed SF prostaglandin E2 and substance P release at PIH 8 and bradykinin at PIH 24 compared to placebo treatment. General MMP activity at PIH 8 and 24 was significantly lower in meloxicam- vs. placebo-treated joints, as were GAG, C2C and CPII concentrations at PIH 24. Conclusions: Acute transient synovitis leads to substantial increases in SF biomarkers of inflammation, MMP activity and cartilage turnover, which can be significantly suppressed by meloxicam. Conclusions: Early oral treatment with meloxicam ameliorates not only clinical signs and joint inflammation in acute synovitis, but may also limit inflammation-induced cartilage catabolism.
Publication Date: 2009-11-26 PubMed ID: 19927589DOI: 10.2746/042516409x436286Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article analyzes the effects of a commonly used nonsteroidal anti-inflammatory drug, meloxicam, on joint inflammation and cartilage turnover in horses. It finds that meloxicam significantly reduces inflammation markers, MMP activity and cartilage turnover in horses suffering from acute synovitis.

Study Objective and Methods

  • The aim of the study was to assess the impact of meloxicam on inflammatory markers, matrix metalloproteinase (MMP) activity, and cartilage indicators in horse joints with experimentally induced synovitis.
  • A cross-over study was conducted involving six horses, where acute synovitis (joint inflammation) was induced with an intra-articular injection of lipopolysaccharide (an endotoxin).
  • The horses were then given either a placebo or meloxicam daily, post injection.
  • Samples of blood and synovial fluid (joint fluid) were collected at different post-injection hours (PIH) and analyzed for a range of markers.

Results

  • Injection of lipopolysaccharide resulted in significant, but transient, synovitis without systemic effects.
  • Administering meloxicam led to a notable reduction in lameness at PIH 8 and 24 and a slight decrease in joint swelling.
  • The release of inflammatory markers prostaglandin E2 and substance P in the synovial fluid were significantly reduced with the administration of meloxicam at PIH 8, compared to a placebo treatment, as was bradykinin at PIH 24.
  • Meloxicam-treated joints exhibited less general MMP activity and lowered concentrations of cartilage markers glycosaminoglycans, type II collagen cleavage fragments and type II collagen carboxypropeptide at PIH 24, compared to placebo-treated joints.

Conclusions

  • Transient synovitis can result in substantial increases in synovial fluid biomarkers of inflammation, MMP activity, and cartilage turnover. However, these can be significantly lowered with meloxicam.
  • Early oral treatment with meloxicam not only alleviates clinical signs and joint inflammation in acute synovitis, but may also limit the breakdown of cartilage induced by inflammation.

Cite This Article

APA
de Grauw JC, van de Lest CH, Brama PA, Rambags BP, van Weeren PR. (2009). In vivo effects of meloxicam on inflammatory mediators, MMP activity and cartilage biomarkers in equine joints with acute synovitis. Equine Vet J, 41(7), 693-699. https://doi.org/10.2746/042516409x436286

Publication

ISSN: 0425-1644
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 41
Issue: 7
Pages: 693-699

Researcher Affiliations

de Grauw, J C
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
van de Lest, C H A
    Brama, P A J
      Rambags, B P B
        van Weeren, P R

          MeSH Terms

          • Animals
          • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
          • Biomarkers
          • Cartilage, Articular / drug effects
          • Cartilage, Articular / metabolism
          • Cartilage, Articular / pathology
          • Horse Diseases / drug therapy
          • Horse Diseases / metabolism
          • Horse Diseases / pathology
          • Horses
          • Inflammation / drug therapy
          • Inflammation / metabolism
          • Inflammation / veterinary
          • Lameness, Animal
          • Meloxicam
          • Metalloproteases / analysis
          • Metalloproteases / metabolism
          • Synovial Fluid / chemistry
          • Synovitis / drug therapy
          • Synovitis / metabolism
          • Synovitis / pathology
          • Thiazines / therapeutic use
          • Thiazoles / therapeutic use

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